In the last article we guided you through the history of modern medicine’s understanding of the endocannabinoid system. We were met with a rather strange surprise ending for both the scientific and medical cannabis communities. Put simply, the focus of the entire medical cannabis movement had been cannabis itself; the plant and medicines produced via refining that plant. Yet, the underlying reason that cannabis is such an effective medicine is found in the body’s own endocannabinoid system. This system is activated not only through externally applied exocannabinoids, such as those in smoked or vaporized cannabis, but also the body’s own naturally-produced endocannabinoids, and finally by artificially produced cannabinoid receptor activators. The star of the show is not cannabis at all but the endocannabinoid system, which is activated through numerous pathways. Cannabis just happens to have been mankind’s first interaction with being able to affect, manipulate, and repair the body’s own endocannabinoid system. In that way, humans are very lucky for this unlikely intersection of evolution, where a chemical group a plant produces for its own benefit coincides with a chemical group that the human body uses to regulate itself. The cannabis plant still remains one of the cheapest and most energy efficient ways to produce cannabinoids that would require more complex and costly resources to produce in a laboratory setting. Because of this efficiency, the cannabis plant will likely continue to play a large role in the medical community even after more direct, more controllable means of directing the endocannabinoid system are possible. In this article, we will conduct a brief review of general areas in which the endocannabinoid system has shown medicinal value.
Anxiety research has shown that the two cannabinoid receptors, CB1 and CB2, are both capable of decreasing anxiety when activated. Since CB1 receptors are grown more densely in the brain than CB2 receptors, CB1 receptors and their receptor activators have been the focus of most anxiety research. However, readers should be aware that almost all research has indicated that CB receptor activation is biphasic. Biphasic is a term used to describe a substance that produces opposite behaviors at different doses. In other words, a moderate amount of THC may alleviate anxiety, whereas an extreme dose may heighten anxiety and lead to paranoia. This is one reason that all medical cannabis patients should experiment with dosing (titration); despite the mental trap of thinking that more medicine leads to more healing, the truth is that more is not always better.
One issue remaining with treating anxiety with cannabis is that cannabinoids are applied all throughout the brain, rather than produced on the spot, exactly when and where needed. The ability to target a specific area of the brain would decrease unwanted side-effects, while also treating anxiety in a way that is much more native to the brain than blood-borne cannabinoids. For this reason, some research has focused on experimenting with blocking the enzymes that break apart or remove cannabinoids, which would allow the level of cannabinoids to increase only where they are already being produced.
Sadly, the most damning proof that the endocannabinoid system receptors are tied deeply to an emotional state and depression came in the form of Rimonabant, a discontinued weight loss drug manufactured by Sanofi-Aventis. Noting the ability of cannabinoid receptor activation to increase appetite, Aventis developed a drug to completely block the receptor to achieve the opposite result. Although the drug was technically “successful” at reducing appetite, it also led to suicidal thoughts, depression, and anxiety in many patients, despite the fact that all patients had been screened prior to the study to ensure no history of mental illness or depression. While this was a costly, unfortunate experiment for many patients, it also gave researchers the chance to see the consequences of deactivating the endocannabinoid system on a large scale.
The endocannabinoid system has also been shown to impair short-term, working memory, while leaving long-term memory intact. Multiple rodent tests have confirmed that rodents with increased levels of CB receptor activation show delays in memory recall as well as hampered new memory formation. This memory loss is related to other changes in brain function and thought patterns, but appears to be reversible and to only occur during periods of cannabinoid use, with cannabinoid cessation leading to recovered ability. Furthermore, evidence seems to indicate that moderate cannabinoid receptor activation can actually protect memory loss during older age. Regardless, medical cannabis patients should consider all the research especially when medicating during memory-intensive tasks.
Outside of its receptors, the endocannabinoid system is capable of affecting the body in even more numerous ways. Cannabidiol (CBD) is one cannabinoid not produced within the body that does not normally bind to either cannabinoid receptor, CB1 or CB2. However, it does function as a direct antagonist or limiter to molecules that do activate those receptors. This is why high-CBD strains are generally attributed as “creeper” or delayed onset as the CBD delays the onset of THC. CBD may also have some interaction with the brain’s modulation of serotonin and has already shown value in its own right in various anti-inflammatory roles all throughout the body. In other words, it is important to remember that the body is more than the sum of its parts, and the presence and impact of the endocannabinoid system in the brain goes beyond mere activation of its receptors. What we are seeing now is the tip of the iceberg in terms of understanding how cannabinoids, endocannabinoids, and various other molecules relate to a system now confirmed beyond doubt to play a large role in all of our lives.
Raphael Mechoulam and Linda A. Parker. (2012) The Endocannabinoid System and the Brain. Annual Review of Psychology (2013) 64:21-47.